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. Author manuscript; available in PMC: 2024 Nov 5.
Published in final edited form as: Eur J Med Chem. 2023 Jul 11;259:115632. doi: 10.1016/j.ejmech.2023.115632

Table 1.

Enzyme inhibition activities from two-point and ten-point dose response screenings of selected electrophilic fragments at caspase-2 and caspase-3.

Cmp d. Casp2 Inhibiti on at 12.5 μM [%]a Casp2 Inhibiti on at 6.25 μM [%]a Casp3 Inhibiti on at 125 μM [%]a Casp3 Inhibiti on at 62.5 μM [%1a pIC50 ± SEMa selectivity: kinact/Ki (Casp2) [M−1 s−1]b
Casp2 N Casp3 N IC50 (Casp3 ) / IC50 (Casp2)
12 84 62 91 80 5.57 ± 0.01 2 < 4.30 2 > 19 n.d.
17 92 86 90 59 5.97 ± 0.03 2 4.54 ± 0.01 2 27 4.49 × 104
46 93 92 30 24 5.89 ± 0.01 2 5.02 ± 0.08 2 7 5.86 × 104
97 89 79 16 10 5.74 ± 0.03 2 4.45 ± 0.05 2 19 7.97 × 104
118 77 56 0 5 5.43 ± 0.01 2 < 4.20 2 > 17 4.60 × 101
166 83 68 92 32 5.56 ± 0.04 2 4.41 ± 0.05 2 14 n.d.
196 90 86 96 96 6.15 ± 0.06 2 5.14 ± 0.05 2 10 4.37 × 102
239 86 70 80 36 5.50 ± 0.01 2 < 4.30 2 > 16 n.d.
294 92 82 88 53 5.66 ± 0.01 2 4.50 ± 0.03 2 14 n.d.
750 85 70 86 46 5.49 ± 0.02 2 < 4.00 2 > 31 n.d.
1269 79 62 14 0 5.50 ± 0.04 2 < 4.30 2 > 16 6.32 × 105
1532 90 79 59 18 5.50 ± 0.02 2 < 4.00 2 > 32 n.d.
1598 71 53 0 1 5.31 ± 0.01 2 < 4.00 2 > 20 5.21 × 104
1715 60 62 69 23 5.31 ± 0.01 2 < 4.00 2 > 20 n.d.
1765 66 57 52 6 5.38 ± 0.01 2 < 4.00 2 > 24 n.d.
a

pIC50 values and single dose inhibition values were obtained based on measurements at 40 min. Data shown are mean values ± SEM of N independent experiments, each performed in duplicate. Data were analyzed by nonlinear regression and were best fitted to sigmoidal concentration-response curves (variable slope, four parameter fit).

b

kinact/Ki values were calculated in two-steps by obtaining kobs values first (a) Irreversible Inactivation and b) Two Step Irreversable Secondary Regression (Copeland 9.2)) and using kinetic data of at least four different inhibitor concentrations. n.d. = not determined.